title: Attenuation of glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant gene activation.
abstract: OBJECTIVE
  Nuclear factor erythroid 2-related factor 2 (Nrf2) is a positive regulator of the expression of antioxidant genes. This study is aimed at examining the effect of tert-butylhydroquinone (tBHQ), an activator of Nrf2, on hyperglycemia-related diabetic nephropathy.
  
  
  METHODS
  CD-1 mice were induced with streptozotocin and treated with 1% tBHQ, or omitting it, in their diet for 12 weeks. Four and twelve weeks later, the levels of serum and glomerular malondialdehyde (MDA), blood glucose, kidney and body weights, and proteinuria were measured. The pathogenic process in the kidney was examined histologically and by transmission electron microscopy. The relative levels of Nrf2, heme oxygenase-1 (HO-1), γ-glutamylcysteine synthethase (γ-GCS) expression and nuclear accumulation of Nrf2 in the glomeruli were determined by reverse transcription polymerase chain reaction and Western blot assays.
  
  
  RESULTS
  In the glomeruli of diabetic mice, treatment with tBHQ significantly reduced the levels of serum and glomerular MDA, kidney weight and proteinuria, decreased fibronectin accumulation and mitigated the pathogenic processes. It also enhanced Nrf2, HO-1 and γ-GCS expression and Nrf2 nuclear accumulation.
  
  
  CONCLUSIONS
  tBHQ has beneficial effects on reducing hyperglycemia-induced kidney injury, which is associated with the enhanced expression of Nrf2, and its downstream antioxidant HO-1 and γ-GCS in the glomeruli of diabetic mice.
authors.affiliation: Departments of Histology and Embryology, Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Lianshan
authors.initials: L
authors.lastname: Zhang
authors.forename: Fuxu
authors.initials: F
authors.lastname: Wang
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Shi
authors.forename: Yunzhuo
authors.initials: Y
authors.lastname: Ren
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Yanping
authors.initials: Y
authors.lastname: Cao
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism; D007678:Kidney Glomerulus / Q000293:injuries / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; D008315:Malondialdehyde; C018855:2-tert-butylhydroquinone; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase